Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies
Brain, Volume 133, No. 6, Year 2010
Notification
URL copied to clipboard!
Description
Hereditary neuropathies form a heterogeneous group of disorders for which over 40 causal genes have been identified to date. Recently, dominant mutations in the transient receptor potential vanilloid 4 gene were found to be associated with three distinct neuromuscular phenotypes: hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy and congenital distal spinal muscular atrophy. Transient receptor potential vanilloid 4 encodes a cation channel previously implicated in several types of dominantly inherited bone dysplasia syndromes. We performed DNA sequencing of the coding regions of transient receptor potential vanilloid 4 in a cohort of 145 patients with various types of hereditary neuropathy and identified five different heterozygous missense mutations in eight unrelated families. One mutation arose de novo in an isolated patient, and the remainder segregated in families. Two of the mutations were recurrent in unrelated families. Four mutations in transient receptor potential vanilloid 4 targeted conserved arginine residues in the ankyrin repeat domain, which is believed to be important in protein-protein interactions. Striking phenotypic variability between and within families was observed. The majority of patients displayed a predominantly, or pure, motor neuropathy with axonal characteristics observed on electrophysiological testing. The age of onset varied widely, ranging from congenital to late adulthood onset. Various combinations of additional features were present in most patients including vocal fold paralysis, scapular weakness, contractures and hearing loss. We identified six asymptomatic mutation carriers, indicating reduced penetrance of the transient receptor potential vanilloid 4 defects. This finding is relatively unusual in the context of hereditary neuropathies and has important implications for diagnostic testing and genetic counselling. © The Author (2010).
Authors & Co-Authors
Baets, Jonathan
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Antwerpen
Universiteit Antwerpen
Belgium, Edegem
Universitair Ziekenhuis Antwerpen
Auer-Grumbach, Michaela
Austria, Graz
Medizinische Universität Graz
Merlini, Luciano
Italy, Ferrara
University of Ferrara
Italy, Bologna
Irccs Rizzoli Orthopaedic Institute, Bologna
Hilton-Jones, David
United Kingdom, Oxford
John Radcliffe Hospital
McEntagart, Meriel E.
United Kingdom, London
St George’s, University of London
Crosby, Andrew H.
United Kingdom, London
St George’s, University of London
Barišić, Nina
Croatia, Zagreb
University of Zagreb
Boltshauser, Eugen J.
Switzerland, Zurich
Universität Zürich
Shaw, Christopher E.
United Kingdom, London
King's College London
Landouré, Guida
United Kingdom, London
University College London
United States, Bethesda
National Institutes of Health Nih
Ludlow, Christy L.
United States, Harrisonburg
James Madison University
Gaudet, Rachelle
United States, Cambridge
Harvard University
Houlden, Henry H.
United Kingdom, London
Ucl Queen Square Institute of Neurology
United Kingdom, London
Medical Research Council
Reilly, Mary M.
United Kingdom, London
Medical Research Council
Fischbeck, Kenneth H.
United States, Bethesda
National Institutes of Health Nih
Sumner, Charlotte Jane
United States, Baltimore
Johns Hopkins University
Timmerman, Vincent
Belgium, Antwerpen
Universiteit Antwerpen
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Statistics
Citations: 103
Authors: 17
Affiliations: 20
Identifiers
Doi:
10.1093/brain/awq109
ISSN:
14602156
Research Areas
Cancer
Disability
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study